This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bipolar disorder is characterized by recurrent episodes of mania and depression, a common psychiatric disorder. This disorder affects about 2.3 million adults every year in the US, costing $44 billion annually, but less than half of these patients are treated successfully. The mood stabilizer, lithium, has proven its efficacy in preventing the recurrence of mania and suicide more than any other drug for more than 50 years. In the past decade, however, lithium use in the United States has declined substantially, a trend not seen in the rest of the world. One of the reasons for this is the perception that lithium is more difficult to use. Additionally, only a subpopulation of patients shows benefits from lithium treatment, and therapeutic effects may not be fully apparent for several months. Therefore, it would be beneficial if there were a simple, rapid, and reliable assay that can be applied prior to treating patients with the drug to predict which patients will show a therapeutic response to lithium. Bipolar disorder patients with a family history of the disorder respond to lithium treatment better than those without such a family history, suggesting that lithium sensitivity is controlled in part by genetic factors. Since gene mutations affect not only the cells of the brain but also peripheral cells, lithium sensitivity may be predicted using peripheral cells. In the past, numerous studies have been conducted on gene expression by lithium stimulation in rodents and humans. The observation that lithium affects gene expression patterns in a variety of cells suggests that monitoring gene expression in human peripheral cells may provide a comprehensive diagnostic for patients'responsiveness to lithium. However, due to the lack of any animal or cell model regarding lithium sensitivity, no study exists in which differential gene expression is reported between lithium responders and nonresponders. Therefore, the goal of our present proposal is to identify a set of marker genes that are differentially expressed between lithium : responders and non-responders, and test our hypothesis that clinical response to lithium can be predicted using gene expression patterns in human peripheral cells. In addition to the P.I., the proposed study will be conducted by a team, which consists of the Functional Genomics Core Facility at MSM, and Dr. Ghaemi, Tufts Medical Center, MA. The proposed study will be an element within our bipolar disorder sleep-wake cycle study, in which we already have access to skin samples of bipolar patients.